Spinocerebellar Ataxia 12 (PPP2R2B)
| Dred_ID | RD00030 |
| OMIM ID | 604326 |
| Disease name | Spinocerebellar Ataxia 12 |
| Alternative names | SCA12 |
| Category | Genetic diseases, Rare diseases, Neuronal diseases, Skin diseases, Eye diseases, Mental diseases, Ear diseases, Metabolic diseases, Fetal diseases, Liver diseases |
| Phenotype | NIH Rare Diseases: Spinocerebellar ataxia type 12 (SCA12) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by the presence of action tremor associated with relatively mild cerebellar ataxia. Associated pyramidal and extrapyramidal signs and dementia have been reported.EpidemiologyPrevalence is unknown. Approximately 40 families have been reported.Clinical descriptionThe age of symptomatic onset ranges from 8 to 55 years with most patients presenting in the 4th decade.EtiologyLike SCA8 the pathogenesis of SCA12 seems to be related to a toxic effect at the RNA level as it is caused by a CAG expansion at the 5' end of the PPP2R2B gene on chromosome 5q31-5q32.PrognosisPrognosis is essentially good. In many cases progression of the illness is slow and in general life expectancy is not affected.Visit the Orphanet disease page for more resources.
OMIM: Spinocerebellar ataxia type 12 (SCA12) is characterized by onset of action tremor of the upper extremities in the fourth decade, slowly progressing to include ataxia and other cerebellar and cortical signs. Given the small number of individuals known to have SCA12, it is possible that other clinical manifestations have not yet been recognized. |
| Miscellaneouse | OMIM: age at onset 8 to 55 years (mean 40 years) normal cag repeat length is 7 to 32 triplets pathogenic cag repeat length is 51 to 78 triplets |
| Prevalence | Prevalence: <1/1000000 (Worldwide) [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | PPP2R2B |
| Alias symbols | PR52B; SCA12; B55BETA; PR55BETA; PP2ABBETA; PP2APR55B; PR2ABBETA; PR55-BETA; PP2AB55BETA; PR2AB55BETA; PP2APR55BETA; PR2APR55BETA |
| Gene name | protein phosphatase 2, regulatory subunit B, beta |
| Gene map locus | 5q32; chr5:146,580,742-147,084,784(-) |
| Ensembl Gene ID | ENSG00000156475 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | The product of this gene belongs to the phosphatase 2 regulatory subunit B family. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a beta isoform of the regulatory subunit B55 subfamily. Defects in this gene cause autosomal dominant spinocerebellar ataxia 12 (SCA12), a disease caused by degeneration of the cerebellum, sometimes involving the brainstem and spinal cord, and in resulting in poor coordination of speech and body movements. Multiple alternatively spliced variants, which encode different isoforms, have been identified for this gene. The 5' UTR of some of these variants includes a CAG trinucleotide repeat sequence (7-28 copies) that can be expanded to 55-78 copies in cases of SCA12. [provided by RefSeq, Jul 2016] |
| Repeat unit | CAG |
| Normal repeat copies | 7-32 |
| Pathogenic repeat copies | ≥51 |
| Gene | PPP2R2B |
| Repeat location | intron |
| Chromosome locus | chr5:146878726-146878758 (-) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | The current data suggest at least two nonmutually exclusive hypotheses of SCA12 neurodegeneration. First, the repeat may influence PPP2R2B expression, by altering promoter activity, splicing, or transcript stability. This hypothesis would predict that the mutation changes the regulation of protein phosphatase 2A, with implications for the phosphoproteome. Alternatively, the repeat itself may be expressed and have toxic properties, though perhaps not through polyglutamine tracts. Either hypothesis may provide novel insight into the pathogenesis of neurodegeneration. [By PMID: 27748686] |
| Pathway annotation | Reactome, KEGG |
| PMID | 20533062 |
| Authors | Lin CH, Chen CM, Hou YT, Wu YR, Hsieh-Li HM, Su MT, Lee-Chen GJ |
| Title | The CAG repeat in SCA12 functions as a cis element to up-regulate PPP2R2B expression |
| Journal | Hum Genet. 128(2):205-12 |
| Year | 2010 |
| PMID | 21827912 |
| Authors | O'Hearn E, Holmes SE, Margolis RL |
| Title | Spinocerebellar ataxia type 12 |
| Journal | Handb Clin Neurol. 103:535-47 |
| Year | 2012 |